O-Desmethyl Venlafaxine (ODV), chemically known as 4-[2-dimethylamino-1-(1-hydroxy-cyclohexyl)-ethyl]-phenol is a major metabolite of venlafaxine. It is represented by the structural formula V as shown below.

In vivo studies suggest that ODV is a more potent inhibitor of nor-epinephrine and serotonin uptake than venlafaxine. An imbalance among neurotransmitters is the cause of depression. Serotonin and norepinephrine are two neurotransmitters released by nerves in the brain. Desvenlafaxine works by preventing the reuptake of serotonin and epinephrine by nerves after they have been released. Since uptake is an important mechanism for removing released neurotransmitters and terminating their actions on adjacent nerves, the reduced uptake caused by desvenlafaxine increases the effect of serotonin and norepinephrine in the brain, which helps to maintain mental balance and thus desvenlafaxine is mainly useful to control depression.
Venlafaxine and ODV were first claimed and processes for their preparation were disclosed in U.S. Pat. No. 4,535,186. The process is represented as shown below in the Scheme 1.

The process involves debenzylation of benzylated venlafaxine by catalytic hydrogenation. However, preparation of benzylated venlafaxine involves in situ generation of aluminium hydride, by reacting lithium aluminium hydride with concentrated sulphuric acid. Handling these reagents on a plant scale is very difficult and hazardous.
WO2000/059851, WO2002/064543, U.S. Pat. No. 6,689,912, and US2007/0299283 provide alternative processes for preparing ODV, which proceed via the demethylation of venlafaxine. However, these reactions involve, respectively: the use of demethylating agents such as diphenyl phosphine and n-butyllithium; an alkali metal salt of trialkylborohydride; high molecular weight alkane or arene thiolate anions in high boiling point solvents such as PEG-400; and metal sulfides such as sodium sulfide in a solvent 1-methylpyrrolidone. These reagents are expensive, toxic and/or hazardous and require extensive purification procedures to isolate the desvenlafaxine and/or corresponding by-products. The processes give moderate to low yields and impure end products and thus are unsuitable for industrial implementation.
WO2008/093142 discloses a preparation of ODV, which involves debenzylation of 1-[1-(4-benzyloxy-phenyl)-2-dimethylamino-ethyl]-cyclohexanol. However, the preparation of amidocyclohexanol involves the use of strong, non-nucleophilic bulky and sterically hindered bases such as lithium hexamethyl disilazide.
WO2009/084038 discloses a process for the preparation of O-desmethyl-venlafaxine, and pharmaceutically acceptable salts thereof by demethylating venlafaxine or salts using an alkali or alkaline earth metal salt of a mercapto acid or its derivative, such as mercapto alcohols, heterocyclic mercaptans, xanthates, thioacids or mixtures thereof in the presence of an organic solvent.
Thus, there exists a need for an improved process for the preparation of ODV or its pharmaceutically acceptable salts which is safe, short, economical, high yielding, and environmentally friendly, and which avoids the use of potentially hazardous reagents.